Children and adolescents with Klinefelter syndrome: testosterone substitutionKlinefelter syndrome (KS) is the most frequent cause of male hypogonadism in the general population. Early substitution with testosterone is suggested in hypogonadal adult men with KS in order to prevent or correct osteoporosis, abdominal fat deposition, muscle weakness and persistent gynaecomastia. So far, no clear evidence is available with regard to the optimal timing of the onset of testosterone replacement therapy (TRT) in adolescents with KS. Prospective randomized trials in adolescents with KS are thus warranted to establish the need for early testosterone substitution in this young population.